This invention generally relates to analgesic and anti-tumor solutions. Specifically, it pertains to a polarized dilute scorpion venom solution, a method for making a polarized dilute scorpion venom solution, and a method for administering dilute scorpion venom solution. The polarized dilute scorpion venom solution relieves pain, improves immune-system response, treats cancer, prevents cancer, improves quality of sleep, reduces inflammation, and minimizes negative biological response to chemotherapy and radiation treatment.
Around the world, research is being done on the potential effectiveness of scorpion venom as a cancer-fighting tool. Scientists have taken a synthetic version of venom of Leiurus quinquestriatus, also known as the Giant Yellow Israeli scorpion, labeled it with radioactive iodine and found it to be an effective delivery vehicle for targeted radiotherapy against glioma. The synthetic venom binds to glioma cells and has an unusual ability to pass through the blood-brain barrier that blocks most substances from reaching brain tissue from the bloodstream. The synthetic venom is used primarily as a carrier to transport radioactive iodine to glioma cells, but there is data that suggests that it may also slow down the growth of tumor cells.
Dr. M. A. A. Omran of Suez Canal University in Egypt published the study “Cytotoxic and apoptotic effects of scorpion Leiurus quinquestriatus venom on 293T and C2C12 eukaryotic cell lines” in the Journal of Venomous Animals and Toxins including Tropical Diseases. Dr. Omran's study proves the venom from scorpions of the Buthidae family, particularly Leiurus quinquestriatus, produces apoptosis in human cells. The most intriguing element of Dr. Omran's study was that it showed that scorpion venom produces both apoptosis (cellular suicide) and necrosis (cellular death through trauma). The key issue is concentration. At certain concentrations, scorpion venom resulted in apoptosis. In other, larger concentrations, cytotoxicity shifted to necrosis.
Like Leiurus quinquestriatus, Rhopalurus junceus (blue scorpion) belongs to the Buthidae family of scorpions. The blue scorpion is indigenous to Eastern Cuba, Venezuela, Haiti, and the Dominican Republic. Blue scorpion venom, has been used as a folk medicine in Eastern Cuba for generations. It was found that in a certain areas of Cuba when people who had chronic conditions were stung by the blue scorpion, their conditions surprisingly improved instead of getting worse. In 1980, blue scorpion venom was researched in the Cuban province of Guantanamo, one of the areas where the blue scorpion is indigenous. Originally the chemicals taken from the blue scorpion were used primarily to treat ailments in animals. The effects upon animals were found to be extraordinary. Doctors then began to consider the positive impact it could have upon the health of humans. In the early 1990's, blue scorpion venom was tested on a human patient and was found to shrink, and then eliminate, the tumor of a young Cuban woman. Ever since that event it has been in use as an aggressive treatment for anti-tumor therapy.
Recently, blue scorpion venom has been shown to have a variety of health benefits including powerful analgesic and anti-inflammatory effects. In addition to cancer, blue scorpion venom has been shown to have positive results with a wide variety of immune-system related diseases including: HIV; Alzheimer's Disease; Multiple Sclerosis; Muscular Dystrophy; and Arthritis. During the last 15 years, over 60,000 people outside the United States have taken blue scorpion venom and witnessed great improvements in their lives.
Although blue scorpion venom has been used in the past to treat pain, inflammation, cancer, and other ailments the delivery systems and scorpion venom solutions themselves have been inconsistent. This made administration of an effective blue scorpion venom solution difficult. Thus, there is a need in the art for a blue scorpion venom solution that is stable, safe, effective, and consistent.
Moreover, blue scorpion venom, like many liquids, is most effective when it is polarized.
A polarized liquid, as compared to non-polarized liquid, is absorbed far more rapidly into the human body and is significantly more bio-available on a cellular level, resulting in significantly improved results. This has been tested in small scale blind studies in which the cases did not know whether or not they were receiving unpolarized liquid or polarized liquid. In those cases where individuals actually received polarized/magnetized liquid, they reported significantly improved results over those individuals who received non-polarized liquid. It is believed that the effects of the polarization process stays effectively within the liquid for three to four weeks before the liquid returns to a state similar to pre-polarization. To polarize scorpion venom, the venom is repeatedly exposed to fixed magnetic fields aligns the magnetic poles of the molecules within the scorpion venom liquid in such a way that it forms a geometric consistency between the molecules which influences the body's ability to recognize the liquid and open molecular gates for better absorption. This process preferably utilizes fixed magnets; however, electromagnets may also be used. This process is an integral part of the solution and method of the current invention and is explained in more detail below.
Currently, scorpion venom solutions are not available in a polarized liquid form. Thus, there is a need in the art for a polarized blue scorpion venom solution and a method for making polarized blue scorpion venom solution.
As discussed above, blue scorpion venom provides benefits to the human body through apoptosis. Apoptosis is a biological mechanism through which cytotoxicity takes place. Apoptosis diminishes unhealthy inflammatory response, improves efficacy of chemotherapy, supports growth of healthy cellular tissue, and is essential to the body's natural ability to destroy cancerous tumors.
The process of apoptosis a major focus of research and the development of new pharmaceutical drugs for the treatment of: cancer; HIV; arthritis; multiple Sclerosis; Alzheimer's Disease; a wide range of other auto-immune conditions; and supporting appropriate immune system response to organ transplants.
Because apoptosis is the primary mechanism by which blue scorpion venom relieves pain, improves immune-system response, treats cancer, prevents cancer, improves quality of sleep, reduces inflammation, and minimizes negative biological response to chemotherapy and radiation treatment, an expanded understanding of apoptosis is required. The role of cellular suicide in the formation of embryonic cells has been recognized for a great deal of time, but what was not understood was the crucial role cellular suicide plays in healthy biological function. The differences between cellular suicide and necrosis are well documented. Necrosis occurs when a cell becomes acutely injured and ruptures, causing inflammatory cells to rush in to clear away the debris. Programmed cell suicide, in contrast, is clean, quick, and involves a predictable sequence of structural changes that cause a cell to shrink and then be rapidly digested by neighboring cells. This programmed cell suicide process is called apoptosis.
Additionally, research has been done that shows that apoptosis is genetically controlled. Furthermore, the link between apoptosis and cancer is well established.
Over the last 20 years, using emerging technologies, scientists have confirmed that apoptosis plays a central role within developing organisms by shaping the neural and immune systems and molding tissue specificity. They also demonstrated that apoptosis helps to establish a natural balance between cell death and cell renewal in mature animals by destroying excess, damaged, or abnormal cells. Mounting evidence indicates that the acquired ability to resist apoptosis is a hallmark of most, and perhaps all, types of cancer. As scientists learn more about how apoptosis is thwarted by cancer, they are also gaining a greater understanding of why many tumors are resistant to the cellular suicide-inducing effects of radiation and chemotherapy. Researchers are exploring how apoptosis is regulated and how it can be selectively triggered, through tailored treatments, to induce suicide in cancer cells while leaving healthy cells alone.
To better understand apoptosis, necrosis must also be understood. Cells that are damaged by injury, such as by mechanical damage or exposure to toxic chemicals, undergo a characteristic series of changes, including: they (and their organelles, like mitochondria) swell (because the ability of the plasma membrane to control the passage of ions and water is disrupted); and the cell contents leak out, leading to inflammation of surrounding tissues.
By contrast cells that are induced to commit suicide (apoptosis): shrink; develop bubble-like blebs on their surface; have the chromatin (DNA and protein) in their nucleus degraded; have their mitochondria break down with the release of cytochrome c; break into small, membrane-wrapped, fragments; the phospholipid phosphatidylserine, which is normally hidden within the plasma membrane, is exposed on the surface; the cell fragments are bound by receptors on phagocytic cells like macrophages and dendritic cells, which then engulf the cell fragments; and the phagocytic cells secrete cytokines that inhibit inflammation (e.g., IL-10 and TGF-β). The line of events in death by suicide is so orderly that the process is often called programmed cellular death.
There are two different reasons why cells typically commit suicide. First, programmed cell death is as needed for proper development as mitosis is. For example: the resorption of the tadpole tail at the time of its metamorphosis into a frog occurs by apoptosis; the formation of the fingers and toes of the fetus requires the removal, by apoptosis, of the tissue between them; the sloughing off of the inner lining of the uterus (the endometrium) at the start of menstruation occurs by apoptosis; and the formation of the proper connections (synapses) between neurons in the brain requires that surplus cells be eliminated by apoptosis. Second, programmed cell death is needed to destroy cells that represent a threat to the integrity of the organism. For example: cells infected with viruses. Indeed, one of the methods by which cytotoxic T lymphocytes (CTLs) kill virus-infected cells is by inducing apoptosis. Moreover, as cell-mediated immune responses wane, the effector cells must be removed to prevent them from attacking body constituents. CTLs induce apoptosis in each other and even in themselves. Defects in the apoptotic machinery are associated with autoimmune diseases such as lupus erythematosus and rheumatoid arthritis.
Cells with DNA damage. Damage to its genome can cause a cell to disrupt proper embryonic development leading to birth defects or become cancerous. Cells respond to DNA damage by increasing their production of a protein called p53. p53 is a potent inducer of apoptosis. Mutations in the p53 gene frequently cause a defective protein to be produced. These mutated p53 genes are often found in cancer cells and these cancer cells represent a lethal threat to the organism if permitted to live.
Cancer cells. Radiation and chemicals used in cancer therapy induce apoptosis in some types of cancer cells. Radiation and chemotherapy cause apoptosis by withdrawing positive signals; that is, signals needed for continued survival, or by sending negative signals.
Withdrawal of positive signals. The continued survival of most cells requires that they receive continuous stimulation from other cells and, for many, continued adhesion to the surface on which they are growing. Some examples of positive signals: growth factors for neurons; and Interleukin-2 (IL-2), an essential factor for the mitosis of lymphocytes.
Receipt of negative signals cause: increased levels of oxidants within the cell; damage to DNA by these oxidants or other agents like ultraviolet light, x-rays, and chemotherapeutic drugs; accumulation of proteins that failed to fold properly into their proper tertiary structure; molecules that bind to specific receptors on the cell surface and signal the cell to begin the apoptosis program. These death activators include: tumor necrosis factor-alpha (TNF-α) that binds to the TNF receptor; lymphotoxin (also known as TNF-β) that also binds to the TNF receptor; and Fas ligand (FasL), a molecule that binds to a cell-surface receptor named Fas (also called CD95).
The Mechanisms of Apoptosis. There are 3 different mechanisms by which a cell commits suicide by apoptosis. The first is generated by signals arising within the cell (internal signals). The second is triggered by death activators binding to receptors at the cell surface, such as TNF-α, Lymphotoxin, and Fas ligand (FasL). The third is reactive oxygen.
Apoptosis triggered by internal signals involves the intrinsic or mitochondrial pathway. In a healthy cell, the outer membranes of its mitochondria display the protein Bcl-2 on their surface. Internal damage to the cell (e.g., from a reactive oxygen species) causes Bcl-2 to activate a related protein, Bax, which punches holes in the outer mitochondrial membrane, causing cytochrome c to leak out. The released cytochrome c binds to the protein Apaf-1 (“apoptotic protease activating factor-1”). Using the energy provided by ATP, these complexes aggregate to form apoptosomes. The apoptosomes bind to and activate caspase-9. Caspase-9 is one of a family of over a dozen caspases. They are all proteases. They get their name because they cleave proteins, mostly each other, at aspartic acid (Asp) residues. Caspase-9 cleaves and, in so doing, activates other caspases (caspase-3 and -7). The activation of these “executioner” caspases creates an expanding cascade of proteolytic activity (rather like that in blood clotting and complement activation) which leads to digestion of structural proteins in the cytoplasms, degradation of chromosomal DNA, and phagocytosis of the cell.
Apoptosis triggered by external signals involves the extrinsic or death receptor pathway. Fas and the TNF receptor are integral membrane proteins with their receptor domains exposed at the surface of the cell, binding of the complementary death activator (FasL and TNF respectively) transmits a signal to the cytoplasm that leads to activation of caspase 8. Vaspase 8 (like caspase 9) initiates a cascade of caspase activation leading to phagocytosis of the cell.
When cytotoxic T cells recognize (bind to) their target, they produce more FasL at their surface. This binds with the Fas on the surface of the target cell leading to its death by apoptosis.
Apoptosis-inducing factor (AIF) is a protein that is normally located in the inter-membrane space of mitochondria. When the cell receives a signal telling it that it is time to die, AIF is released from the mitochondria (like the release of cytochrome c in the first pathway); migrates into the nucleus; binds to DNA, which triggers the destruction of the DNA and cell death.
Apoptosis and Cancer. Some viruses associated with cancers use tricks to prevent apoptosis of the cells they have transformed. Several human papilloma viruses (HPV) have been implicated in causing cervical cancer. One of them produces a protein (E6) that binds and inactivates the apoptosis promoter p53. Epstein-Barr Virus (EBV), the cause of mononucleosis and associated with some lymphomas, produces a protein similar to Bcl-2 and produces another protein that causes the cell to increase its own production of Bcl-2. Both these actions make the cell more resistant to apoptosis (thus enabling a cancer cell to continue to proliferate). Even cancer cells produced without the participation of viruses may have tricks to avoid apoptosis. Some B-cell leukemias and lymphomas express high levels of Bcl-2, thus blocking apoptotic signals they may receive. The high levels result from a translocation of the BCL-2 gene into an enhancer region for antibody production. Melanoma (the most dangerous type of skin cancer) cells avoid apoptosis by inhibiting the expression of the gene encoding Apaf-1. Some cancer cells, especially lung and colon cancer cells, secrete elevated levels of a soluble “decoy” molecule that binds to FasL, plugging it up so it cannot bind Fas. Thus, cytotoxic T cells (CTL) cannot kill the cancer cells by the mechanism shown above. Other cancer cells express high levels of FasL, and can kill any cytotoxic T cells (CTL) that try to kill them because CTL also express Fas (but are protected from their own FasL).
Apoptosis in the Immune System. The immune response to a foreign invader involves the proliferation of lymphocytes, T and/or B cells. When their job is done, they must be removed leaving only a small population, of memory cells. This is done by apoptosis. Very rarely humans are encountered with genetic defects in apoptosis. The most common one is a mutation in the gene for Fas, but mutations in the gene for FasL or even one of the caspases are occasionally seen. In all cases, the genetic problem produces autoimmune lymphoproliferative syndrome or ALPS. The features of ALPS include: an accumulation of lymphocytes in the lymph nodes and spleen greatly enlarging them; the appearance of clones that are autoreactive, that is, attack “self” components producing such autoimmune disorders as hemolytic anemia and thrombocytopenia; and the appearance of lymphoma, a cancerous clone of lymphocytes. In most patients with ALPS, the mutation is present in the germline; that is, every cell in their body carries it. In a few cases, however, the mutation is somatic; that is, has occurred in a precursor cell in the bone marrow. These later patients are genetic mosaics, with some lymphocytes that undergo apoptosis normally and others that do not. The latter tend to out-compete the former and grow to become the major population in the lymph nodes and blood.
Apoptosis and AIDS. HIV (human immunodeficiency virus) invades CD4+ T cells, and one might assume that it this infection by HIV that causes the great dying-off of these cells. However, that appears not to the main culprit. Fewer than 1 in 100,000 CD4+ T cells in the blood of AIDS (acquired immunodeficiency syndrome) patients are actually infected with the virus any uninfected CD4+ cells. The hallmark of AIDS is the decline in the number of the patient's CD4+ T cells (normally about 1000 per microliter (μl) of blood). CD4+ T cells are responsible, directly or indirectly (as helper cells), for all immune responses. When their number declines below about 200 per μl, the patient is no longer able to mount effective immune responses and begins to suffer a series of dangerous infections. The cause of the disappearance of CD4+ T cells is clear: apoptosis. The actual mechanism is not as clear. One mechanism may be: all T cells, both infected and uninfected, express Fas; the expression of a HIV gene (called Nef) in a HIV-infected cell causes the cell to express high levels of FasL at its surface while preventing an interaction with its own Fas from causing it to self-destruct. However, when the infected T cell encounters an uninfected one (e.g. in a lymph node), the interaction of FasL with Fas on the uninfected cell kills it by apoptosis.
Apoptosis and organ transplants. For many years it has been known that certain parts of the body such as the anterior chamber of the eye and the testes have antigens that fail to elicit an immune response. This finding raises the possibility of a new way of preventing graft rejection. If at least some of the cells on a transplanted kidney, liver, heart, etc. could be made to express high levels of FasL, which might protect the graft from attack by the T cells of the host's cell-mediated immune system. If so, then the present need for treatment with immunosuppressive drugs for the rest of the transplant recipient's life would be reduced or eliminated. So far, the results in animal experiments have been mixed. Allografts engineered to express FasL have shown increased survival for kidneys but not for hearts or islets of Langerhans.
Apoptosis activation as a therapeutic strategy for cancer. Cell survival is maintained by a balance between pro-apoptotic and anti-apoptotic stimuli. Dysregulation of apoptosis can disrupt the equilibrium between cell growth and cell death and is an important step in the development of cancer. It is this understanding that has led to the investigation of therapeutic activation of apoptosis in cancer cells as a potential anticancer strategy.
The role of p53 protein in apoptosis. Chemotherapy/radiotherapy-induced and p53-mediated activation of apoptosis via the intrinsic signaling pathway. As prior research has found, the tumor suppressor protein p53 is one of many proteins that contributes to the activation of the intrinsic signaling pathway. Inactivation of this protein or elements of its attendant pathway (upstream activators and/or downstream effectors), due to mutation, is seen in as many as half of all human cancers. Because of the important role of p53 in the intrinsic apoptosis pathway, such a mutation can render tumor cells resistant to conventional radio- and chemotherapy. Current conventional therapies such as radio- and chemotherapy indirectly promote apoptosis, although this is an important endpoint of the therapeutic effect. These regimens induce apoptosis by causing DNA damage. In doing so, they stimulate apoptosis through the intrinsic pathway.
Apoptosis independent of p53. Promoting the alternative “extrinsic” apoptosis pathway, which operates independently of p53, or augmenting downstream elements of the intrinsic apoptosis pathway, may have the potential to induce apoptosis both in cancer cells that are responsive and in those cancer cells that have become resistant to conventional therapies.
Apoptosis and naturally occurring chemicals. It has been shown that a variety of naturally occurring chemicals trigger apoptosis in humans, including Vitamins C and D. Extensive research has also shown that curcumin, a chemical from the culinary herb turmeric, also induces apoptosis in humans. In recent years, a tremendous amount of pharmaceutical research has turned its focus to natural venoms. Venoms of any kind are particularly intensely bioactive substances. Recently, peptides taken from the poison of the cone snail (Conus parius) have been approved by the FDA to be used as a treatment for chronic pain. These peptides, in the right concentration, have been shown to work as effectively as morphine, but without any addictive qualities. Venom of the scorpion Leiurus quinquestriatus, from the Buthidae family, has had a great deal of research associated with its efficacy in treating brain cancer. A great amount of research has been done over the last 15 years regarding scorpions of the Buthidae family and it has been shown, to varying degrees, that the venom from this family produces apoptosis in humans when administered in appropriate concentrations.
This research led to the present invention, a polarized dilute scorpion venom solution, a method for making a polarized dilute scorpion venom solution, and a method for administering dilute scorpion venom solution. The polarized dilute scorpion venom solution relieves pain, improves immune-system response, treats cancer, prevents cancer, improves quality of sleep, reduces inflammation, and minimizes negative biological response to chemotherapy and radiation treatment.